mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1927 - 1946

Published: Jan. 1, 2024

The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane.However, the molecular mechanism which sevoflurane activates remains unclear.The cGAS-STING pathway an evolutionarily conserved inflammatory defense mechanism.The role sevoflurane-induced inflammasome-dependent and underlying mechanisms require further investigation.We found that prolonged anesthesia with triggered characterized vivo.Interestingly, was activated hippocampus mice receiving sevoflurane.While blockade cGAS RU.521 attenuated mice.In vitro, we treatment significantly microglia, while pre-treatment robustly inhibited activation.Mechanistically, mitochondrial fission released DNA (mtDNA) into cytoplasm, could be abolished Mdivi-1.Blocking mtDNA release via mPTP-VDAC channel inhibitor cytosolic escape reduced finally inhibiting activation.Therefore, regulating targeting may provide a novel therapeutic target POCD.

Language: Английский

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CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 13, 2024

Abstract Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer’s due to their covalently closed loop structure. However, involvement circRNAs postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted whole transcriptome sequencing initially this study. According expression profiles, observed that circAKT3 was associated with hippocampal neuronal apoptosis mice. Moreover, found overexpression reduced neurons alleviated POCD. Subsequently, through bioinformatics analysis, our data showed vitro vivo elevated abundance miR-106a-5p significantly, resulting a decrease HDAC4 protein an increase MEF2C protein. Additionally, effect blocked by inhibitor. Interestingly, could activate transcription promoter form positive feedback loop. Therefore, findings revealed more potential modulation ways circRNA-miRNA miRNA-mRNA, providing different directions targets for preclinical studies

Language: Английский

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Assessment of Antimicrobial, Cytotoxic and Antioxidant Potentials of n-Hexane, Chloroform and Ethyl Acetate Extracts of Sonneratia apetala Banks Fruits

Biomedical & Pharmacology Journal, Journal Year: 2025, Volume and Issue: 18(1), P. 581 - 591

Published: March 31, 2025

This study evaluated the antioxidant, antimicrobial and cytotoxic activities of different fractions from ethanolic crude extract Sonneratia apetala fruits (Family: Lythraceae). Antimicrobial activity was assessed using disc diffusion method with ciprofloxacin fluconazole as reference standards. Among fractions, chloroform fraction demonstrated mild to moderate (8-20 mm zone inhibition), highest against Pseudomonas aeruginosa (20 mm) a minimum inhibitory concentration (MIC) 32 µg. The lethality test for brine shrimp used assess cytotoxicity, showing LC50 values 22.41 µg/ml (n-hexane), 20.53 (chloroform), 24.60 (ethyl acetate), compared vincristine sulfate (8.66 µg/ml). Antioxidant activity, determined via DPPH radical scavenging, revealed IC50 42.03 13.76 49.99 ascorbic acid standard (IC50 45.47 amount total phenolic content detected in (26.88 mg GAE/g extract). These findings suggest S. possesses significant antioxidant potential, alongside activity.

Language: Английский

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The Critical Role of Sirt1 in Subarachnoid Hemorrhages: Mechanism and Therapeutic Considerations

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(4), P. 674 - 674

Published: April 18, 2023

The subarachnoid hemorrhage (SAH) is an important cause of death and long-term disability worldwide. As a nicotinamide adenine dinucleotide-dependent deacetylase, silent information regulator 1 (Sirt1) multipotent molecule involved in many pathophysiological processes. A growing number studies have demonstrated that Sirt1 activation may exert positive effects on SAHs by regulating inflammation, oxidative stress, apoptosis, autophagy, ferroptosis. Thus, agonists serve as potential therapeutic drugs for SAHs. In this review, we summarized the current state our knowledge relationship between provided updated overview downstream molecules

Language: Английский

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Tibetan medicine Ruyi Zhenbao Pill ameliorates neuropathic pain by inhibiting the CXCL10-CXCR3 pathway in spinal cord of spinal nerve ligation model

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 323, P. 117653 - 117653

Published: Dec. 30, 2023

Language: Английский

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Urinary metabolomic analysis of three fundamental traditional Mongolian Medicine Constitution types using UHPLC-QTOF-MS and nuclear magnetic resonance techniques

Journal of Radiation Research and Applied Sciences, Journal Year: 2024, Volume and Issue: 17(2), P. 100915 - 100915

Published: April 14, 2024

Human constitution is closely linked to health and disease serves as a basis for diagnosis. In this work, the urinary metabolomics of three basic traditional Mongolian medicine (MMC) types were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) nuclear magnetic resonance (NMR) techniques. 90 volunteers majoring in from university during 2021.1–2023.1 averagely grouped based on characteristics MMC Classification Scoring Scale Medicine Constitution: Khii group, Shar Badgan group. NMR technology was employed determine metabolites subjects different groups. UHPLC-QTOF-MS applied identify differential urine. Multivariate statistical analysis (MSA) including principal component (PCA), partial least squares-discriminant (PLS-DA), orthogonal (OPLS-DA) adopted analyze impacts metabolites. positive ion mode exhibited higher signal intensity better separation efficiency. Accuracy exceeded 99%. PCA demonstrated satisfactory clustering results. Covered metabolic pathways encompassed tricarboxylic acid cycle (TCA), fatty beta-oxidation, well protein, nucleic acid, amino metabolisms. constitutions may involve several small molecular (SMMs) like bile acids, carnitine, aromatic carboxylic acids. When clinically diagnosing treating diseases constitution, constitutional factors should be considered.

Language: Английский

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Depletion of PIEZO1 expression is accompanied by upregulating p53 signaling in mice with perioperative neurocognitive disorder

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 23, 2023

Abstract As the common complications observed in surgical elder patients, perioperative neurocognitive disorders (PND) cause a series of serious health problems. However, there are no effective treatments, and exact mechanisms still largely unknown. In this study, transcriptome sequencing was performed to investigate differentially expressed genes (DEGs)in hippocampus C57BL/6J aged mice with or without PND. Compared Mock group, expression 352, 395, 772 changed significantly PND group at day 1, 7, 21 after surgery, respectively. Gene Ontology (GO) Set Enrichment Analysis (GSEA) showed that DEGs were mainly associated p53 signaling. Moreover, GSEA revealed potentially p53-related such as leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1), monooxygenase DBH-like (MOXD1), piezo type mechanosensitive ion channel component (PIEZO1). Furthermore, we confirmed decreased interaction PIEZO1 PND, upregulation resulted decrease protein levels through increased ubiquitination p53. conclusion, study contributes knowledge global changes gene during

Language: Английский

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mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 3, 2023

Abstract Background NLRP3 inflammasome activation is critical for neuroinflammation in microglia during postoperative cognitive dysfunction (POCD) induced by sevoflurane. However, the molecular mechanism which sevoflurane activates remains unclear. The cGAS- STING pathway an evolutionarily conserved inflammatory defense mechanism. role of cGAS-STING sevoflurane-induced inflammasome-dependent and underlying mechanisms require further investigation. Methods Prolonged anesthesia with was used to induce mice. passive avoidance test Y-maze were assess function. We then cGAS inhibitor RU.521 investigate whether involved mice microglia. To sevoflurane-treated microglia, we pre-treated Mdivi-1 (a DRP1 inhibitor), CsA mPTP inhibitor) or VBIT-4 VDAC inhibitor). Results found that prolonged triggered characterized inflammasome. Interestingly, activated hippocampus receiving While blockade attenuated In vitro , treatment significantly while pre-treatment robustly inhibited activation. Mechanistically, mitochondrial fission released DNA (mtDNA) into cytoplasm, could be abolished Mdivi-1. Blocking mtDNA release via mPTP-VDAC channel cytosolic escape reduced finally inhibiting Conclusion this study, reported a novel POCD. Therefore, regulating targeting may provide therapeutic target

Language: Английский

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Depletion of PIEZO1 expression is accompanied by upregulating p53 signaling in mice with perioperative neurocognitive disorder

Functional & Integrative Genomics, Journal Year: 2023, Volume and Issue: 23(4)

Published: Oct. 27, 2023

Language: Английский

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